Comparison of total midgut volvulus and segmental volvulus in neonates.

BACKGROUND: Intestinal volvulus in a neonate, complete or segmental, is a true surgical emergency, which when the diagnosis is delayed can bring detrimental results. The aim of this study was to describe the clinical characteristics of intestinal volvulus during the neonatal period by comparing total midgut volvulus (TMV) and segmental volvulus (SV). METHODS: The medical records of 44 neonates who were operated on for intestinal volvulus from 1993 to 2019 were retrospectively reviewed. The patients were divided into TMV and SV groups, and clinical features were compared. RESULTS: Operations were performed on 27 patients for TMV and 17 for SV. All cases of TMV were associated with intestinal malrotation, while those with SV were not. Gestational age, birth weight, and ratio of prematurity showed no differences between the groups. Preoperative diagnosis of TMV or SV was possible in 23 and 5 (85% and 29%) cases, respectively. Intestinal resection was required in 16/17 patients (94%) with SV, while it was required in 5/27 (19%) patients with TMV. When bowel resection was performed in TMV, all but one patient suffered from short bowel syndrome leading to two mortalities, while SV group showed good recovery. CONCLUSION: Diagnosis of SV before laparotomy can be difficult. Even though performing intestinal resection in SV neonates is highly likely, it shows a favorable outcome. TMV neonates are less likely to undergo intestinal resection; however, when bowel ischemia is present, significant morbidity can occur. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level IV.

Body mass index and skeletal muscle index are useful prognostic factors for overall survival after gastrectomy for gastric cancer: Retrospective cohort study.

Among patients undergoing gastrectomy for gastric cancer, the impact of anthropometric indices on surgical outcomes is not well-established. The aim of this study was to evaluate the prognostic significance of the skeletal muscle index (SMI) and body mass index (BMI) on overall survival (OS) in patients with gastric cancer.A total of 305 patients who underwent curative gastrectomy for gastric adenocarcinoma between January 2005 and March 2008 were enrolled. Patients were classified into groups based on the SMI and BMI. The SMI was measured by preoperative abdominal computed tomography (CT). The SMI groups were classified based on gender-specific cut-off values obtained by means of optimum stratification. BMI groups were divided according to the World Health Organization definition of obesity for Asians.The mean SMI was 58.2 cm/m and the mean BMI was 23.2 kg/m. One hundred fifteen (37.7%) patients had sarcopenia based on the diagnostic cut-off values (56.2 cm/m for men and 53.6 cm/m for women). Apart from gender, there were no significant differences in patient characteristics or surgical outcomes between the SMI groups. In the underweight group, tumor (T) stage, tumor-node-metastasis (TNM) stage, number of retrieved lymph nodes, D2 dissection, and hospital stay were significantly increased compared with the overweight/obese group. High and low BMI, and low SMI, were independent prognostic factors for OS (hazard ratio [HR] = 2.355, 1.736, and 1.607, respectively; P = .009, .023, and .033, respectively).SMI and BMI did not impact perioperative morbidity in patients undergoing gastrectomy for gastric cancer. Both SMI and BMI are useful prognostic factors for OS in gastric cancer patients after gastrectomy.

Prediction of postoperative mortality and morbidity in octogenarians with gastric cancer - Comparison of P-POSSUM, O-POSSUM, and E-POSSUM: A retrospective single-center cohort study.

BACKGROUND: The purpose of this study was to evaluate various POSSUM scoring systems in predicting postoperative morbidity and mortality in elderly patients with gastric cancer. METHODS: A total of 1262 patients with gastric cancer who underwent curative gastrectomy between January 2006 and December 2013 were retrospectively reviewed. The subjects were stratified by age into <80 years old and ≥80 years old. To assess the predictability and efficacy of various POSSUM scores (POSSUM, P-POSSUM, O-POSSUM, and E-POSSUM), the observed-to-expected (O:E) ratio and area under the receiver operating characteristic curve (AUC) were calculated and compared with actual postoperative morbidity and mortality. RESULTS: Among the 1262 patients, 75 were elderly (≥80 years old). The observed mortality rates were 0.5% (n = 6) in the whole cohort, and 4.0% (n = 3) in elderly patients. The predicted mortalities of POSSUM, P-POSSUM, E-POSSUM, and O-POSSUM for elderly patients were 13.2%, 5.3%, 5.7%, and 21.8%, respectively (O:E ratio = 0.3, 0.75, 0.7, and 0.18, respectively). P-POSSUM and E-POSSUM showed superior discriminatory power compared to POSSUM and O-POSSUM. In terms of morbidity, E-POSSUM showed better predictive capabilities than POSSUM in elderly patients (O:E ratio = 0.56 and 0.74, respectively). CONCLUSIONS: All POSSUM scoring systems tend to overestimate postoperative mortality and morbidity in gastric cancer patients. E-POSSUM and P-POSSUM provided a better prediction of mortality and morbidity after curative gastrectomy in elderly patients compared to other POSSUM scores.

Expression patterns of programmed death-1 and programmed death-1 ligand-1 on T cells in gastric cancer.

The aim of the present study was to evaluate programmed death-1 (PD-1) and programmed death-1 ligand-1 (PD-L1) expression in gastric carcinoma and to assess their effect on survival rate. A total of 170 surgically resected specimens were obtained from patients diagnosed with gastric carcinoma at St. Vincents Hospital, The Catholic University of Korea. Paraffin tissue sections from tissue microarray blocks were subjected to immunohistochemical analysis of PD-1 and PD-L1. In addition, PD-1 expression on CD4+ and CD8+ T cells isolated from peripheral blood mononuclear cells and gastric cancer tissues was evaluated by multicolor flow cytometry. PD-1 and PD-L1 were expressed in 30.0 and 60.5% of the gastric cancer tissues, respectively. The expression of PD-L1 was higher in patients with advanced T (P=0.035) and Tumor, Node and Metastasis stage (P=0.05). The patients with positive PD-L1 expression had shorter disease-free survival time than those without PD-L1 expression (P=0.005). Additionally, PD-L1 expression was significantly associated with poor prognosis (P=0.015). PD-1 and PD-L1 expression levels were significantly higher on CD8+ T cells than on CD4+ T cells (P<0.001). The data of the present study suggested that PD-L1 expression may be an independent indicator of poor prognosis in patients with gastric cancer. Furthermore, PD-L1 expression may play a role in immune evasion of gastric cancer.

Genomic structures of dysplastic nodule and concurrent hepatocellular carcinoma.

Although high-grade dysplastic nodule (HGDN) is a preneoplastic lesion that precedes hepatocellular carcinoma (HCC), the genomic structures of HGDN in conjunction with HCC remain elusive. The objective of this study was to identify genomic alterations of HGDN and its difference from HCC that may drive HGDN progression to HCC. We analyzed 16 regions of paired HGDN and HCC from 6 patients using whole-exome sequencing to find somatic mutation and copy number alteration (CNA) profiles of HGDN and HCC. The numbers of mutations, driver mutations, and CNAs of HGDNs were not significantly different from those of HCCs. We identified that the CNA gain of 1q25.3-1q42.13 was predominant in the HCCs compared with that in the HGDNs. Two cases (one nodule-in-nodule case and another case with closely attached HCC and HGDN) showed several overlapped driver mutations (CTNNB1 and CEBPA) and CNAs (losses of CDKN2A, RB1, and TP53) between HGDNs and HCCs, suggesting their roles in the early HCC development. The other 4 cases with spatially separated HCCs and HGDNs showed few overlapped alterations between the paired HCCs and HGDNs. Mutations in ERBB2 and CCND1, and CNAs (gains of CTNNB1, MET, and SMO and losses of PTEN, TP53, and SETD2) were identified as "HCC predominant," suggesting their roles in the progression of HGDN to HCC. Our data show that HCCs are direct descendants of HGDNs in some cases, but there is no direct evidence of such relationship in spatially separated cases. Genomic features of HGDN identified in this study provide a useful resource for dissecting clues for the genetic diagnosis of HGDN and HCC.

A missense mutation in EBF2 was segregated with imperforate anus in a family across three generations.

The etiology of imperforate anus, a major phenotype of anorectal malformation (ARM), is still unknown and not a single gene has been reported to be associated with it. We studied a Korean family with six affected members with imperforate anus across three generations by whole exome sequencing and identified a missense mutation in the EBF2 gene (c.215C > T; p.Ala72Val). This mutation is completely segregated with the disease phenotype in the family and is evolutionarily highly conserved among diverse vertebrates. Also, this mutation was predicted to be functionally damaging. These results support that missense mutation in the EBF2 c.215C > T (p.Ala72Val) is very likely to contribute to the pathogenesis of ARM in this family.

Genomic profiles of a hepatoblastoma from a patient with Beckwith-Wiedemann syndrome with uniparental disomy on chromosome 11p15 and germline mutation of APC and PALB2.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder mainly associated with altered genomic imprinting at chromosome 11p15.5. Children with BWS, especially uniparental disomy (UPD) at 11p15.5, are at increased risk of embryonal tumors including hepatoblastoma. Although genetic alterations of sporadic hepatoblastomas have been identified, integrated germline and somatic alterations of BWS-related hepatoblastoma have not been reported. For this, we performed whole-exome sequencing and genome-wide loss of heterozygosity/copy number analyses using a single nucleotide polymorphism (SNP) array for a hepatoblastoma in a BWS infant with paternal UPD at chromosome 11p15.5. We found germline 11p15.5 UPD as well as germline mutations of APC and PALB2 in the patient. At the somatic level, we found a CTNNB1 hotspot mutation and chromosome 1q gain in the tumor. The development of hepatoblastoma in this case might be explained by predisposition of the germline events (11p15.5 UPD, mutations of APC and PALB2) and later by somatic events with CTNNB1 somatic mutation and 1q gain. To our knowledge, this is the first report of germline and somatic genomic alteration profiles in hepatoblastoma arising from BWS. Clinically, our results provide a rationale for performing a more strict and intense protocol for hepatoblastoma surveillance in a high-risk BWS infant, such as the UPD-carrying case, for early detection and treatment.

Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer.

Although ductal carcinoma in situ (DCIS) precedes invasive ductal carcinoma (IDC), the related genomic alterations remain unknown. To identify the genomic landscape of DCIS and better understand the mechanisms behind progression to IDC, we performed whole-exome sequencing and copy number profiling for six cases of pure DCIS and five pairs of synchronous DCIS and IDC. Pure DCIS harbored well-known mutations (e.g., TP53, PIK3CA and AKT1), copy number alterations (CNAs) and chromothripses, but had significantly fewer driver genes and co-occurrence of mutation/CNAs than synchronous DCIS-IDC. We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC. Of note, synchronous DCIS genomes were closer to IDC than pure DCIS. Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations. Our results indicate that although pure DCIS has already acquired some drivers, more changes are needed to progress to IDC. In addition, IDC-associated DCIS is more aggressive than pure DCIS at genomic level and should really be considered IDC. Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes.